Virus-like particles of retroviral origin in protein aggregation and neurodegenerative diseases

IF 8.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Aspects of Medicine Pub Date : 2025-05-20 DOI:10.1016/j.mam.2025.101369

Serena Carra , Balazs Fabian , Hamed Taghavi , Edoardo Milanetti , Valeria Giliberti , Giancarlo Ruocco , Jason Shepherd , Michele Vendruscolo , Monika Fuxreiter

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引用次数: 0

Abstract

A wide range of human diseases are associated with protein misfolding and amyloid aggregates. Recent studies suggest that in certain neurological disorders, including Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD) and various tauopathies, protein aggregation may be promoted by virus-like particles (VLPs) formed by endogenous retroviruses (ERVs). The molecular mechanisms by which these VLPs contribute to protein aggregation, however, remain enigmatic. Here, we discuss possible molecular mechanisms of ERV-derived VLPs in the formation and spread of protein aggregates. An intriguing possibility is that liquid-like condensates may facilitate the formation of both protein aggregates and ERV-derived VLPs. We also describe how RNA chaperoning, and the encapsulation and trafficking of misfolded proteins, may contribute to protein homeostasis through the elimination of protein aggregates from cells. Based on these insights, we discuss future potential therapeutic opportunities.

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蛋白质聚集和神经退行性疾病中源自逆转录病毒的病毒样颗粒

许多人类疾病都与蛋白质错误折叠和淀粉样蛋白聚集有关。最近的研究表明，在某些神经系统疾病中，包括肌萎缩侧索硬化症（ALS）、额颞叶痴呆（FTD）和各种牛头病，内源性逆转录病毒（erv）形成的病毒样颗粒（vlp）可能促进蛋白质聚集。然而，这些VLPs促进蛋白质聚集的分子机制仍然是谜。在这里，我们讨论了erv衍生的VLPs在蛋白质聚集体形成和扩散中的可能分子机制。一种有趣的可能性是，液体状凝聚物可能促进蛋白质聚集体和erv衍生的VLPs的形成。我们还描述了RNA陪伴，以及错误折叠蛋白质的封装和运输，如何通过消除细胞中的蛋白质聚集体来促进蛋白质稳态。基于这些见解，我们讨论了未来潜在的治疗机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Aspects of Medicine 医学-生化与分子生物学

CiteScore

18.20

自引率

0.00%

发文量

审稿时长

55 days

期刊介绍： Molecular Aspects of Medicine is a review journal that serves as an official publication of the International Union of Biochemistry and Molecular Biology. It caters to physicians and biomedical scientists and aims to bridge the gap between these two fields. The journal encourages practicing clinical scientists to contribute by providing extended reviews on the molecular aspects of a specific medical field. These articles are written in a way that appeals to both doctors who may struggle with basic science and basic scientists who may have limited awareness of clinical practice issues. The journal covers a wide range of medical topics to showcase the molecular insights gained from basic science and highlight the challenging problems that medicine presents to the scientific community.